Microfluidic device and a method for provision of double emulsion droplets

Abstract

The present invention relates to a microfluidic device, a method for manufacturing a microfluidic device, and a method for provision of double emulsion droplets using a microfluidic device. Furthermore, the present invention relates to an assembly configured to supply pressure to the microfluidic device for provision of double emulsion droplets. Furthermore, the present invention relates to a kit comprising a plurality of microfluidic devices and a plurality of fluids configured for use with the microfluidic device for provision of double emulsion droplets. The microfluidic device comprises a transfer conduit comprising a first transfer conduit part having a first affinity for water; and a collection conduit comprising a first collection conduit part having a second affinity for water being different from the first affinity for water. A well section and a microfluidic section of the microfluidic device are fixedly connected to each other.

The invention claimed is: 
     
       1. A microfluidic device for production of double emulsion droplets comprising:
 a microfluidic section comprising a plurality of microfluidic units; and 
 a well section comprising a plurality of groups of wells comprising one group of wells for each microfluidic unit; 
 each microfluidic unit comprising a fluid conduit network comprising: 
 a plurality of supply conduits comprising a primary supply conduit, a secondary supply conduit, and a tertiary supply conduit; 
 a transfer conduit comprising a first transfer conduit part having a first affinity for water, wherein the first affinity for water is hydrophobic; 
 a collection conduit comprising a first collection conduit part having a second affinity for water being different from the first affinity for water, wherein the second affinity for water is hydrophilic; 
 a first fluid junction providing fluid communication between the primary supply conduit, the secondary supply conduit, and the transfer conduit, the first transfer conduit part extending from the first fluid junction; and 
 a second fluid junction providing fluid communication between the tertiary supply conduit, the transfer conduit, and the collection conduit, the first collection conduit part extending from the second fluid junction; 
 each group of wells comprising a plurality of wells comprising a collection well and a plurality of supply wells comprising a primary supply well and a tertiary supply well, 
 the well section and the microfluidic section being fixedly connected to each other such that each group of wells being fixedly connected to a respective corresponding microfluidic unit, wherein for each group of wells: 
 the collection well is in fluid communication with the collection conduit of the corresponding microfluidic unit; 
 the primary supply well is in fluid communication with the primary supply conduit of the corresponding microfluidic unit; 
 the tertiary supply well is in fluid communication with the tertiary supply conduit of the corresponding microfluidic unit; and 
 one supply well of the plurality of supply wells is in fluid communication with the secondary supply conduit of the corresponding microfluidic unit, 
 wherein the microfluidic device is configured for containing liquids in an amount required for the provision of droplets as well as the resulting droplets, and further wherein the microfluidic device is a single use device and produces double emulsion droplets. 
 
     
     
       2. The microfluidic device according to  claim 1 , wherein the first transfer conduit part and the first collection conduit part of each microfluidic unit are configured to retain their respective affinity for water for at least one month of storage from time of provision of the respective conduit parts. 
     
     
       3. The microfluidic device according to  claim 1 , wherein the first transfer conduit part or the first collection conduit part of each microfluidic unit is provided by a coating. 
     
     
       4. The microfluidic device according to  claim 3 , wherein the microfluidic section comprises a base microfluidic piece providing at least a part of each of: the primary supply conduit of each microfluidic unit; the secondary supply conduit of each microfluidic unit; the tertiary supply conduit of each microfluidic unit; the transfer conduit of each microfluidic unit; the collection conduit of each microfluidic unit; the first fluid junction of each microfluidic unit; and the second fluid junction of each microfluidic unit; and wherein:
 the base microfluidic piece is provided in a base material having surface properties corresponding to the first affinity for water, wherein at least a part of the coating providing the first collection conduit part is provided on top of the base material of the base microfluidic piece; or 
 the base microfluidic piece is provided in a base material having surface properties corresponding to the second affinity for water, wherein at least a part of the coating providing the first transfer conduit part is provided on top of the base material of the base microfluidic piece. 
 
     
     
       5. The microfluidic device according to  claim 1 , wherein, for each microfluidic unit, the cross-sectional area of any opening between any supply conduit and the first fluid junction is smaller than 2500 μm 2 . 
     
     
       6. The microfluidic device according to  claim 1 , wherein, for each microfluidic unit, the cross-sectional area of an opening between the first fluid junction and the transfer conduit is smaller than 2500 μm 2 . 
     
     
       7. The microfluidic device according to  claim 1 , wherein, for each microfluidic unit, the cross-sectional area of an opening between the first fluid junction and the transfer conduit is between 50% and 100% of the cross-sectional area of an opening between the second fluid junction and the collection conduit. 
     
     
       8. The microfluidic device according to  claim 1 , wherein the microfluidic section comprises a first planar surface and a capping piece comprising a second planar surface, the first planar surface having a plurality of ramified recesses providing a base part of each fluid conduit network of the microfluidic device, the second planar surface facing the first planar surface and providing a capping part of each fluid conduit network of the microfluidic device. 
     
     
       9. The microfluidic device according to  claim 8 , wherein one, more, or all parts of each fluid conduit network form an acute trapezoidal cross section, wherein the longer base edge is provided by the second planar surface of the capping piece. 
     
     
       10. The microfluidic device according to  claim 9 , wherein each acute trapezoidal cross section forms an isosceles trapezoidal cross section, wherein the side walls of equal length have a tapering of at least 5 degrees and at most 20 degrees with respect to a normal of either of the parallel base edges. 
     
     
       11. The microfluidic device according to  claim 1 , wherein each microfluidic unit comprises:
 a primary filter at or within the primary supply conduit; 
 a secondary filter at or within the secondary supply conduit; and 
 a tertiary filter at or within the tertiary supply conduit. 
 
     
     
       12. The microfluidic device according to  claim 1 , wherein the first transfer conduit part extends at least 500 μm. 
     
     
       13. An assembly comprising a receptor and a pressure distribution structure, the receptor being configured to receive and hold the microfluidic device according to  claim 1 , the pressure distribution structure being configured to supply pressure to the microfluidic device when held by the receptor, the pressure distribution structure comprising:
 a plurality of well manifolds comprising a primary well manifold and a tertiary well manifold; a plurality of line pressure regulators comprising a primary line pressure regulator and a tertiary line pressure regulator; and a main manifold; 
 the primary well manifold being configured to be coupled to each primary supply well of the microfluidic device, 
 the tertiary well manifold being configured to be coupled to each tertiary supply well of the microfluidic device, 
 the primary line pressure regulator being coupled to the primary well manifold, 
 the tertiary line pressure regulator being coupled to the tertiary well manifold, 
 the main manifold being coupled to each well manifold via the respective line pressure regulators. 
 
     
     
       14. A kit comprising:
 one or more of the microfluidic device according to  claim 1 ; and 
 a plurality of fluids configured for use with the microfluidic device according to  claim 1 , the plurality of fluids comprising: a sample buffer; an oil; and a continuous phase buffer; 
 the kit comprising an enzyme and nucleotides. 
 
     
     
       15. The kit according to  claim 14 , wherein the density of the oil is higher than the density of the sample buffer. 
     
     
       16. A method for providing double emulsion droplets, the method comprising use of any of:
 the microfluidic device according to  claim 1 ; or for the provision of double emulsion droplets, and comprising: 
 providing a first fluid to the primary supply well of a first group of wells; 
 providing a second fluid to the one supply well of the first group of wells, which supply well is in fluid communication with the secondary supply conduit of the corresponding microfluidic unit; 
 providing a third fluid to the tertiary supply well of the first group of wells; and providing individual pressure differences between each of the respective supply wells of the first group of wells and the collection well of the first group of wells, such that the pressure within each of the individual supply wells of the first group of wells is higher than within the collection well of the first group of wells. 
 
     
     
       17. A method for manufacturing a microfluidic device according to  claim 1 , the method comprising fixing the well section and the microfluidic section to each other, such that fluid communication is provided between the individual wells of each group of wells via the corresponding respective microfluidic units. 
     
     
       18. The microfluidic device according to  claim 1 , wherein the first affinity for water of said transfer conduit part is hydrophobic and wherein the second affinity for water of said first collection conduit part is hydrophilic and wherein said droplets are double-emulsion droplets. 
     
     
       19. The method according to  claim 16 , wherein the one supply well is the primary supply well, the secondary supply well or the tertiary supply well in fluid communication with the secondary supply conduit.